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Fig. 6. Ablation of FGF8 in the PA endoderm and ectoderm by hoxa3-IRESCre
reveals that endodermal domain-specific FGF8 activity is required for thymic,
parathyroid and aortic valve formation. (A) Sections through neck of E18.5
control. Note the large parathyroid gland (pth) embedded in posterior-lateral
aspect of thyroid (tyr). e, esophagus; tr, trachea. (B-D) Parathyroid ectopy
and/or hypoplasia in Fgf8/hoxa3-IRESCre mutants. c,
clavicle. (E) Wild-type control with normal bi-lobed thymus. (F,G) Thymic
hypoplasia and migration defects in Fgf8/Hoxa3-IRESCre
mutants. (F) Hypoplastic left thymus in association with a right aortic arch
(raa). (G) Monolobed ectopic gland. (H) Cross-section of normal aortic valve
in control animal, anterior is towards the left; note three cusps: right (R),
left (L), posterior (P). (I-K) Bicuspid aortic valves in
Fgf8/Hoxa3-IRESCre mutants. (L) Cross-section through the
right ventricular outflow tract of a control embryo showing the relationship
of the aorta (Ao), pulmonary valve (PV) and right ventricle (RV). (M-O)
Sections through an animal with Tetralogy of Fallot (TOF). (M) Dysplastic PV
and severe subvalvar and infundibular stenosis. (N) Cross-section of the left
ventricular outflow tract (LVOT), right ventricle (RV) and intact ventricular
septum in a wild type animal; there is continuity between the aortic (Ao) and
mitral (mv) valves. Note thickness of right ventricular free wall and
ventricular septum (yellow bidirectional arrows); the heart is fixed in late
systole (mitral valve is closed). (O) The mutant displays overriding aorta
(both the right and left ventricular outflow tracts empty through the aortic
valve), right ventricular hyperplasia with marked increase in thickness of the
right ventricular wall and ventricular septum (yellow bidirectional arrows,
heart in late systole), and a large membranous ventricular septal defect (red
arrowhead).
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